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Focus on antipsychotics and related therapeutic drug monitoring. 专注于抗精神病药物及相关治疗药物的监测。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2023-11-19 DOI: 10.1097/YIC.0000000000000523
Alessandro Serretti
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引用次数: 0
Relationship between clinical efficacy and plasma concentration-dose ratio of risperidone in patients with schizophrenia. 精神分裂症患者利培酮的临床疗效与血浆浓度剂量比的关系。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2023-11-02 DOI: 10.1097/YIC.0000000000000490
Qiuying Chen, Jie Min, Haibo Yin, Wenying Xia, Yimin Shen, Ming Shu

This study aimed to retrospectively explore the relationship between clinical efficacy and plasma concentration-dose ratio of risperidone (RIS) in 252 patients with schizophrenia taking RIS orally. After the same dose of RIS treatment, the plasma concentration of RIS/9-hydroxyrisperidone (9-OH-RIS), the total plasma concentration of RIS, and the ratio of the steady-state plasma concentration to the daily dose of the total active product (C/D) showed individual difference. The RIS plasma concentration was significantly higher in patients taking high doses than those taking lower doses ( P  = 0.003). There was a statistically significant difference in C/D ratio between males and females ( P  = 0.003). There were significant differences in ratio of C/D and the total plasma concentration of RIS between patients under 60 years and over 60 years ( P  = 0.016; P  = 0.005). Logistic regression analysis showed that the therapeutic effect and adverse reactions of RIS were correlated with the ratio of C/D in patients with schizophrenia ( P  = 0.038; P  < 0.001). It has been suggested that the importance of monitoring of the plasma concentration of RIS in patients with schizophrenia and the ratio of C/D may be used as the reference for RIS personalized treatment.

本研究旨在回顾性探讨252例精神分裂症患者口服利培酮(RIS)的临床疗效与血浆浓度剂量比的关系。在相同剂量的RIS治疗后,RIS/9-羟基利培酮(9-OH-RIS)的血浆浓度、RIS的总血浆浓度以及稳态血浆浓度与总活性产物日剂量的比率(C/D)显示出个体差异。高剂量组RIS血浆浓度明显高于低剂量组(P = 男女C/D比差异有统计学意义(P = 0.003)。60岁以下和60岁以上患者的C/D比值和RIS总血浆浓度存在显著差异(P = 0.016;P = Logistic回归分析显示RIS的疗效和不良反应与精神分裂症患者C/D比值相关(P = 0.038;P
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引用次数: 1
Capillary blood sampling for the determination of clozapine concentrations: analytical validation and patient experience. 毛细管血液取样测定氯氮平浓度:分析验证和患者经验。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2023-08-07 DOI: 10.1097/YIC.0000000000000494
Bianca D Breken, Koen P Grootens, Annemieke M Vermeulen Windsant-van den Tweel, Walter A Hermens, Hieronymus J Derijks

Patients may be reluctant to start clozapine (CLZ) because of the frequent blood sampling needed for white blood cell monitoring, but also therapeutic drug monitoring of CLZ. Finger prick, instead of venepuncture, might lower the threshold to CLZ use. The aim of this study was to determine whether CLZ concentrations are the same in capillary and venous blood samples. Capillary blood was drawn by finger prick and collected in the Hem-Col tube. Paired capillary and venous blood samples were collected from inpatients and outpatients of a mental health institute. Patients were asked to rate pain, experience, and preference for blood sampling method. Passing-Bablok analysis of 40 paired samples showed that CLZ concentrations were statistically equal in capillary and venous samples {slope 0.96 [95% confidence interval (CI): 0.88-1.04], intercept -6.86 (95% CI: -30.75 to 24.13)}. Venepuncture was the preferred method based on the experience ( P  = 0.009) and preference ( P  = 0.043) items. In conclusion, CLZ concentrations were similar in venous and capillary blood samples. Venepuncture appeared to be preferred to finger prick for blood sampling. Our results emphasize the importance of consulting patients' individual preference for blood sampling method.

患者可能不愿意开始使用氯氮平(CLZ),因为需要频繁采血进行白细胞监测,同时也需要对CLZ进行治疗药物监测。手指刺破,而不是静脉穿刺,可能会降低使用CLZ的门槛。本研究的目的是确定CLZ浓度在毛细血管和静脉血样品中是否相同。采用手指穿刺法抽取毛细血管血,Hem-Col管采集。从精神卫生机构的住院患者和门诊患者中采集配对的毛细血管和静脉血样本。患者被要求对疼痛、经验和对采血方法的偏好进行评分。40个配对样本的passin - bablok分析显示,在毛细血管和静脉样本中CLZ浓度在统计学上相等{斜率0.96[95%可信区间(CI): 0.88-1.04],截距-6.86 (95% CI: -30.75 ~ 24.13)}。根据经验(P = 0.009)和偏好(P = 0.043)项,静脉穿刺是首选方法。结论:大鼠静脉血和毛细血管血CLZ浓度相近。静脉穿刺似乎比手指穿刺更适合采血。我们的研究结果强调了咨询患者对血液采样方法的个人偏好的重要性。
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引用次数: 2
Differentiating the third generation of antipsychotics: a focus on lumateperone's similarities and differences. 区分第三代抗精神病药物:关注鲁马替培隆的异同。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 Epub Date: 2023-09-20 DOI: 10.1097/YIC.0000000000000510
Gloria M Munayco Maldonado, Thomas L Schwartz

The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all dopamine-2 receptor partial agonists with varying receptor affinities. This review aims to compare the clinical and pharmacodynamic differences among these four atypical antipsychotics, all of which are unique when compared to first- and second-generation antipsychotics. For consideration is further delineating these agents as being third-generation antipsychotics. PubMed searches were conducted to compile preclinical and clinical studies derived from animal models and human subjects. Information gathered included pharmacological mechanisms, clinical efficacy, future-oriented clinical approaches, and adverse effects. Efficacy for the shared indications of these drugs seems comparable. Differences among these drugs lie more in their adverse effect profiles. For example, lumateperone was found to have the lowest rate of weight gain while brexpiprazole was found to have the highest rate of weight gain associated with increased appetite. Aripiprazole had the lowest rates of extrapyramidal symptoms not including akathisia while cariprazine had the highest. All four agents reviewed have a variety of receptor affinities, which likely generates a variety of different adverse effects. This suggests that in any given patient, clinicians may see differential clinical effects.

非典型抗精神病药物的发展已经包括了新的药效学特性。Lumateperone、阿立哌唑、布瑞哌唑和cariprazine都是多巴胺-2受体部分激动剂,具有不同的受体亲和力。本综述旨在比较这四种非典型抗精神病药物的临床和药效学差异,与第一代和第二代抗精神病药相比,所有这些药物都是独特的。考虑将这些药物进一步界定为第三代抗精神病药物。PubMed搜索是为了汇编来自动物模型和人类受试者的临床前和临床研究。收集的信息包括药理学机制、临床疗效、面向未来的临床方法和不良反应。这些药物的共同适应症的疗效似乎具有可比性。这些药物之间的差异更多地在于它们的不良反应特征。例如,lumateperone被发现体重增加率最低,而布瑞哌唑被发现与食欲增加相关的体重增加率最高。阿立哌唑的锥体外系症状发生率最低,不包括静坐不起,而卡哌嗪的发生率最高。所审查的所有四种药物都具有各种受体亲和力,这可能会产生各种不同的不良反应。这表明,在任何给定的患者中,临床医生都可能看到不同的临床效果。
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引用次数: 1
Diabetes mellitus in patients with chronic bipolar disorder: prevalence, clinical correlates and relationship with homocysteine. 慢性双相情感障碍患者的糖尿病:患病率、临床相关性及与同型半胱氨酸的关系
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-20 DOI: 10.1097/YIC.0000000000000504
Li Mu, Dachun Chen, Meihong Xiu, Huixia Zhou, Dongmei Wang, Xiang-Yang Zhang

Comorbid diabetes mellitus in patients with bipolar disorder may contribute to increased morbidity and mortality. To determine the prevalence of diabetes mellitus in bipolar disorder patients and its clinico-demographic and homocysteine correlates, we conducted a cross-sectional survey of 195 bipolar disorder inpatients. They received questionnaires, clinical measurements and laboratory tests to assess demographic characteristics, anthropometric variables, clinical variables and plasma homocysteine levels. The prevalence of diabetes mellitus (including type 1, type 2 and special types) in Chinese bipolar disorder patients was 14.9%. Analysis of variance or chi-square test showed that compared with non-diabetic bipolar disorder patients, diabetic bipolar disorder patients were older, more often married, had a longer duration of disease, took less olanzapine and had a higher frequency of hypertension. However, there were no significant differences in body mass index (BMI) and homocysteine levels between diabetic and non-diabetic bipolar disorder patients. Logistic regression analysis showed that marital status and duration of disease were independently associated with diabetes mellitus in patients with bipolar disorder after controlling for age, use of olanzapine, presence of hypertension, BMI and homocysteine levels. These findings shed light on the clinico-demographic correlates of the increased prevalence of diabetes mellitus in bipolar disorder patients, rather than the correlation with some metabolic risk factors.

双相情感障碍患者的合并症糖尿病可能导致发病率和死亡率增加。为了确定糖尿病在双相情感障碍患者中的患病率及其临床人口学和同型半胱氨酸的相关性,我们对195名双相情感障碍住院患者进行了横断面调查。他们接受了问卷调查、临床测量和实验室测试,以评估人口统计学特征、人体测量变量、临床变量和血浆同型半胱氨酸水平。中国双相情感障碍患者中糖尿病(包括1型、2型和特殊型)患病率为14.9%。方差分析或卡方检验显示,与非糖尿病型双相情感障碍患者相比,糖尿病型双相情感障碍患者年龄更大,结婚次数更多,病程更长,服用奥氮平较少,高血压发生率更高。然而,糖尿病和非糖尿病双相情感障碍患者的体重指数(BMI)和同型半胱氨酸水平没有显著差异。Logistic回归分析显示,在控制年龄、是否使用奥氮平、是否存在高血压、BMI和同型半胱氨酸水平后,婚姻状况和病程与双相情感障碍患者糖尿病独立相关。这些发现揭示了双相情感障碍患者中糖尿病患病率增加的临床-人口学相关性,而不是与某些代谢危险因素的相关性。
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引用次数: 0
Spanish versions and validation of a series of rating scales and visual analogue scales to assess the subjective effects of cannabis. 西班牙语版本和一系列评定量表和视觉模拟量表的验证,以评估大麻的主观影响。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-20 DOI: 10.1097/YIC.0000000000000498
Alberto Sainz-Cort, Marta Martín-Islas, Genís Oña, Daniel Jimenez-Garrido, Miriam López-Navarro, Elena Muñoz-Marron, Raquel Viejo-Sobera, Jose Carlos Bouso

Cannabis is being legalized for medical and recreational purposes all around the world. However, the understanding of the psychological effects of cannabis is still limited, and it has been previously linked to mental disorders such as schizophrenia. Lately, new scales have been created and adapted to measure its psychological effects. The aim of this study is to create Spanish versions of some of these scales and test their psychometric characteristics. One hundred sixteen participants were recruited from Cannabis Social Clubs (CSC) in Barcelona, Spain. Participants under the effects of their own cannabis completed the Cannabis Experience Questionnaire-modified version (CEQ-mv), Addiction Research Centre Inventory-18 (ARCI-18), Psychotomimetic States Inventory (PSI) and Visual Analogue Scales (VAS). Questionnaires were completed in the CSC, providing a naturalistic setting for the study. Exploratory factor analysis and internal consistency were analyzed. PSI was reduced from a 6-factor to a 4-factor model with adequate to low reliability, ARCI-18 was reduced from a 3-factor to a 2-factor model with good reliability, and VAS were reduced from a 4-factor to a 3-factor model, also with good reliability. These questionnaires showed adequate reliability and can be used in future studies to test the subjective effects of cannabis in clinical and naturalistic settings.

在世界各地,用于医疗和娱乐目的的大麻正在合法化。然而,对大麻对心理的影响的了解仍然有限,而且它以前被认为与精神分裂症等精神障碍有关。最近,人们创造并调整了新的量表来衡量它的心理影响。本研究的目的是创建其中一些量表的西班牙语版本,并测试它们的心理测量特征。从西班牙巴塞罗那的大麻社交俱乐部(CSC)招募了116名参与者。在自用大麻的影响下,参与者完成了大麻体验问卷修改版(CEQ-mv)、成瘾研究中心清单-18 (ARCI-18)、拟精神状态清单(PSI)和视觉模拟量表(VAS)。问卷在CSC完成,为研究提供了一个自然的环境。探索性因子分析和内部一致性分析。PSI由6因子模型降为4因子模型,信度较低;ARCI-18由3因子模型降为2因子模型,信度较好;VAS由4因子模型降为3因子模型,信度也较好。这些问卷显示出足够的可靠性,并可用于未来的研究,以测试大麻在临床和自然环境中的主观影响。
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引用次数: 0
Neuroscience-based nomenclature as a teaching tool, introduction and pilot study. 基于神经科学的命名法作为一种教学工具,介绍和试点研究。
IF 2.1 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 Epub Date: 2023-04-12 DOI: 10.1097/YIC.0000000000000470
Sasson Zemach, Daniel Minkin Levy, Joseph Zohar

Neuroscience-based nomenclature (NbN) is a pharmacologically-driven nomenclature aiming to replace the current disease-based nomenclature of psychotropics, focusing on pharmacology and mode-of-action to encourage scientifically-minded prescribing. NbN might also be used as a teaching tool as it presents the depth and richness of the neuroscience of psychotropics. This study examines the effect of using NbN in student curriculum. Fifty-six medical students during clerkship in psychiatry, divided into a control group ( n  = 20), taught standard psychopharmacology, and an intervention group ( n  = 36) introduced with NbN. Both groups filled out identical questionnaires at the beginning and end of the clerkship, including questions of knowledge on psychopharmacology, views on current terminology and interest in psychiatric residency. Comparing the average change in scorings (delta post-pre) for each item in intervention vs. control questionnaires, the intervention group showed a significantly larger positive delta in 6 out of 10 items than the control group. Mean scores did not differ significantly between the two groups in the pre-questionnaires, while significantly higher scores were shown for the intervention group in within- and between-group comparisons. Introduction of NbN was associated with a better educational experience, a deeper understanding of psychotropics and increased interest in psychiatric residency.

基于神经科学的命名法(NbN)是一种以药理学为导向的命名法,旨在取代目前以疾病为导向的精神药物命名法,重点关注药理学和作用方式,鼓励以科学的态度开具处方。NbN 还可用作教学工具,因为它展现了精神药物神经科学的深度和丰富性。本研究探讨了在学生课程中使用 NbN 的效果。56 名在精神科实习的医科学生被分为对照组(20 人)和干预组(36 人),对照组教授标准精神药理学,干预组介绍 NbN。两组学生在实习开始和结束时都填写了相同的问卷,其中包括精神药理学知识、对当前术语的看法以及对精神病学实习的兴趣等问题。比较干预组与对照组调查问卷中每个项目的平均得分变化(前后△),发现干预组在 10 个项目中有 6 个项目的正△明显大于对照组。干预组和对照组在预调查问卷中的平均得分没有明显差异,而在组内和组间比较中,干预组的得分明显高于对照组。引入 NbN 与更好的教育体验、加深对精神药物的理解以及提高对精神病学住院医生的兴趣有关。
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引用次数: 0
Ketamine for depression: a potential role in requests for Medical Aid in Dying? 氯胺酮治疗抑郁症:在申请临终医疗救助中的潜在作用?
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 Epub Date: 2023-04-18 DOI: 10.1097/YIC.0000000000000462
Nicolas Garel, Michka Nazon, Kamran Naghi, Elena Willis, Karl Looper, Soham Rej, Kyle T Greenway

Medical Aid in Dying (MAiD) is the act of a healthcare provider ending a patient's life, at their request, due to unbearable suffering from a grievous and incurable disease. Access to MAiD has expanded in the last decade and, more recently, it has been made available for psychiatric illnesses in a few countries. Recent studies have found that such psychiatric requests are rapidly increasing and primarily involve mood disorders as the primary condition. Nevertheless, MAiD for psychiatric disorders is associated with significant controversy and debate, especially regarding the definition and determination of irremediability - that a given patient lacks any reasonable prospect for recovery. In this article, we report the case of a Canadian patient who was actively requesting Medical Assistance in Dying for severe and prolonged treatment-resistant depression until she experienced remarkable benefits from a course of intravenous ketamine infusions. To our knowledge, this is the first report of ketamine or any other intervention yielding remission in a patient who would have otherwise likely been eligible for MAiD for depression. We discuss implications for the evaluation of similar requests and, more specifically, why a trial of ketamine warrants consideration.

临终医疗协助(MAiD)是指医疗服务提供者应病人的要求,在其因严重且无法治愈的疾病而遭受难以忍受的痛苦时结束其生命的行为。在过去的十年中,使用临终关怀的范围不断扩大,最近,在一些国家,精神疾病患者也可以使用临终关怀。最近的研究发现,此类精神病治疗申请正在迅速增加,主要涉及以情绪障碍为主的疾病。尽管如此,精神疾病的 MAiD 仍然存在着巨大的争议和争论,尤其是关于不可救药性的定义和判定--即特定患者缺乏任何合理的康复前景。在这篇文章中,我们报告了一名加拿大患者的病例,她因长期患有严重的难治性抑郁症而积极申请临终医疗协助,直到她从氯胺酮静脉注射疗程中获得了显著的疗效。据我们所知,这是第一份关于氯胺酮或任何其他干预措施使抑郁症患者病情缓解的报告,如果没有氯胺酮或其他干预措施,该患者很可能因抑郁症而符合临终医疗协助的条件。我们讨论了对类似请求进行评估的意义,更具体地说,为什么需要考虑进行氯胺酮试验。
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引用次数: 0
Clinical specificity profile for novel rapid acting antidepressant drugs. 新型速效抗抑郁药物的临床特异性概况。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 Epub Date: 2023-06-30 DOI: 10.1097/YIC.0000000000000488
Mauro Scala, Giuseppe Fanelli, Diana De Ronchi, Alessandro Serretti, Chiara Fabbri

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

情绪障碍是一种复发性/慢性疾病,临床缓解率不尽相同。现有的抗抑郁药物并非对所有患者都有效,而且往往会出现相关的反应潜伏期,并伴有一系列不良反应,包括体重增加和性功能障碍。开发新型快速药物的目的是至少部分克服这些问题。新型药物以谷氨酸、γ-氨基丁酸、奥曲肽和其他受体为靶点,提供了更广泛的药效学机制,即有望增加根据个人临床特征进行个性化治疗的可能性。开发这些新药的目的是将快速作用、可耐受性和对特定症状的更高疗效结合起来,而标准抗抑郁药对这些症状的靶向性相对较差,例如失神和对奖赏的反应、自杀意念/行为、失眠、认知缺陷和易激惹。本综述讨论了新型抗抑郁药物的临床特异性概况,这些药物包括:4-氯炔诺酮(AV-101)、右美沙芬-安非他酮、孕-4-烯-20-炔-3-酮(PH-10)、匹马万塞林、PRAX-114、西洛西宾、艾司美沙酮(REL-1017/右美沙酮)、塞尔特雷克斯坦(JNJ-42847922/MIN-202)和唑拉诺酮(SAGE-217)。主要目的是概述这些化合物对具有不同症状/并发症模式的心境障碍患者的疗效/耐受性,以帮助临床医生在处方这些药物时优化风险/效益比。
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引用次数: 0
Antidepressant emergent mood switch in major depressive disorder: onset, clinical correlates and impact on suicidality. 重度抑郁障碍中的抗抑郁药突发情绪转换:发病、临床相关性及对自杀的影响。
IF 2.6 3区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 Epub Date: 2023-06-09 DOI: 10.1097/YIC.0000000000000479
Paolo Olgiati, Alessandro Serretti

Antidepressant (AD)- emergent mood switch (AEMS) is a common complication of bipolar depression. This study aimed to investigate the prevalence and clinical correlates of subthreshold AEMS (i.e. not fulfilling DSM criteria for hypomanic episodes) in major depressive disorder (MDD) and, prognostically, its impact on AD treatment outcome and suicidality. The study involved 425 outpatients with MDD followed during the acute phase (12 weeks) and continuation (weeks 13-28) AD treatment. AEMS was assessed through the Altman Self-Rating Mania scale (ASRM ≥ 6). Several clinical features differentiated individuals with or without subthreshold AEMS (n = 204 vs. 221): negative self-perception [odds ratio (OR) 1.017-1.565]; panic disorder (OR 1.000-1.091); subthreshold hypomanic episodes (OR 1.466-13.352); childhood emotional abuse (OR 1.053-2.447); lifetime suicidal behaviour (OR 1.027-1.236); AD-related remission (χ 2  = 22.903 P  < 0.0001) and suicide ideation (χ 2  = 16.701 P  < 0.0001). In AEMS earlier onset showed a strong correlation with bipolar spectrum disorder (overall score: P  = 0.0053; mixed depression: P  = 0.0154; subthreshold hypomania: P  = 0.0150) whereas late-onset was associated with more severe suicidal behaviour ( P  < 0.001). In conclusion, our results demonstrate that subthreshold mood switches occur frequently in unipolar depression during acute AD treatment as well as in continuation phase. Time of switch onset seems to have the greatest diagnostic and prognostic value.

抗抑郁剂(AD)-突发情绪转换(AEMS)是双相抑郁症的常见并发症。本研究旨在调查重度抑郁障碍(MDD)中阈下AEMS(即不符合DSM关于躁狂发作的标准)的发生率和临床相关性,以及其对AD治疗效果和自杀倾向的影响。这项研究涉及425名重度抑郁症门诊患者,对他们进行了急性期(12周)和持续期(第13-28周)的AD治疗随访。AEMS通过阿尔特曼躁狂自评量表(ASRM≥6)进行评估。有几个临床特征区分了有或没有阈下AEMS的个体(n = 204 vs. 221):消极的自我认知[几率比(OR)1.017-1.565];惊恐障碍(OR 1.000-1.091);亚阈值躁狂发作(OR 1.466-13.352);童年情感虐待(OR 1.053-2.447);终生自杀行为(OR 1.027-1.236);AD 相关缓解(χ 2 = 22.903 P
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引用次数: 0
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International Clinical Psychopharmacology
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